A Tandem Simulation Approach to Predicting Mapping Quality

2faef7dd62bc570c9fbe5a3620726ff3?s=47 Ben Langmead
October 28, 2016

A Tandem Simulation Approach to Predicting Mapping Quality

Read alignment is the first step in most sequencing data analyses. It is also a source of errors and interpretability problems. Repetitive genomes, algorithmic shortcuts, and genetic variation impede the aligner's ability to find a read's true point of origin. Aligners therefore report a mapping quality: the probability the reported point of origin for a read is incorrect. However, there are no proposals for how to calculate mapping qualities in a general way, applicable across tools and alignment scenarios. I describe an accurate, aligner-agnostic framework for predicting mapping qualities that works by simulating a set of "tandem" reads, similar to the input reads in important ways, but for which the true point of origin is known. Alignments of tandem reads are used to build a model for predicting mapping quality, which is then applied to the input-read alignments. The model is automatically tailored to the alignment scenario at hand, allowing it to make accurate mapping-quality predictions across a range of read lengths, alignment parameters, genomes, and read aligners. I implement this approach in a software tool called Qtip, which is accurate, low-overhead, and compatible with popular read aligners. Qtip is open source software available from https://github.com/BenLangmead/qtip and experiments are published at https://github.com/BenLangmead/qtip-experiments.

2faef7dd62bc570c9fbe5a3620726ff3?s=128

Ben Langmead

October 28, 2016
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